Imidazole → tert-butyl (3R)-3-(iodomethyl)pyrrolidine-1-carboxylate
Reaction equation
[I:1]I.N1C=CN=C1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:28][C@@H:29]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30]1>C(OCC)C.O1CCOCC1>[I:1][CH2:28][C@@H:29]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
Iodine (1.91 g) was added in portions to a vigorously stirred, ice cooled suspension of imidazole (0.681 g) and triphenylphosphine (1.97 g) in diethyl ether (12 mL). The mixture was then stirred for 10 minutes before a solution of tert butyl (R)-3-hydroxymethylpyrrolidine-1-carboxylate (1 g) in dioxane (6 mL) was added dropwise. The resulting mixture was stirred at room temperature overnight, then diluted with diethyl ether and filtered. The solid was washed with diethyl ether and the combined filtrate was evaporated to dryness. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and pentane with a gradient of 0-20% to give tert-butyl (R)-3-iodomethylpyrrolidine-1-carboxylate (1.44 g) as an oil.
Workup
- temperatureice cooled
- additionwas added dropwise
- stirringThe resulting mixture was stirred at room temperature overnight
- filtrationfiltered
- washThe solid was washed with diethyl ether
- customthe combined filtrate was evaporated to dryness
- customThe residue was purified by chromatography on silica
- washeluting with a mixture of ethyl acetate and pentane with a gradient of 0-20%
Sources & evidence
- ORD record
- ord-a1aee225980442869f46cc6d9fe4f392
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09290472B2
Reaction notes
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